PROJECT SUMMARY On a daily basis, sensory stimuli acquire learned values that inform our essential behaviors. Understanding the neural substrates for the emotional associations of stimuli, sometimes referred to as valence, will yield important insights into a wide range of human conditions. This is especially the case for neurodegenerative disorders, including Alzheimer's disease (AD), wherein aberrant assignments of odor valence may impact ingestive behaviors and thus entail malnutrition and subsequent bodily wasting disorders ? further worsening progression of the disease. In the mammalian olfactory system, second order neurons in the olfactory bulb (OB) distribute odor information into several secondary structures, including the olfactory tubercle (OT) and piriform cortex (PCX). Odor information at this stage is shaped and later transmitted into tertiary structures involved in reward, emotion, and learning. The present proposal seeks to assess the impact of AD pathogenesis on the representation of odor valence within the olfactory system and the display of valence-based behaviors. Experiments will be performed taking advantage of a well-established accelerated mouse model of AD, in the context of odor-guided behaviors, and in some cases with simultaneous neural recordings. Using this approach, we will determine whether odor valence is aberrantly reflected across olfactory cortex neural ensembles in the context of AD (Aim 1). Next, we will utilize unbiased, quantitative behavioral and neuroanatomical methods to provide evidence for a relationship between the magnitude of specific components of AD pathology within the OB, OT, and PCX, and the display of odor hedonic behaviors (Aim 2). Together, these investigations will provide much needed information regarding mechanisms underlying reports for diminished odor hedonics in persons with AD.